Blood pressure is regulated to a significant degree by the level of sympathetic nerve activity to the blood vessels. Vasoconstrictor sympathetic preganglionic neurons (SPNs), the source of this activity within the spinal cord, are located within a functionally heterogeneous population of SPNs whose discharge is determined primarily by descending inputs from a few discrete medullary regions. The long-term goal of the proposed research is an understanding of the spinal processing of information in these descending sympathetic pathways to SPNS, particularly with regard to those inputs to SPNs regulating vasoconstriction. Complementary electrophysiological, pharmacologic and electron microscopic studies are planned which examine the functional and structural relationships between splanchnic SPNs and their inputs from the rosaw ventral medulla and the caudal mphe nuclei. Specifically, criteria will be developed to distinguish splanchnic SPNs in the rat which regulate adrenal medullary secretion, visceral vasoconstriction, and gastrointestinal motility. Differences in the responses of these functional classes of SPNs to medullary stimulation will be examined to test the hypothesis that functional specificity exists within descending pathways to splanchnic SPNS. Iontophoretic application of transmitter agonists and antagonists will be used to determine the role of excitatory amino acid transmission in the brainstem stimulus-evoked excitations of SPNs and the potential modulatory functions of medullary catecholaminergic and serotonergic inputs to SPNS. Electron microscopic studies of the inputs to SPNs will combine Phaseolus anterograde labeling of the axon terminals of medullospinal pathways with immunocytochemical detection of transmitter markers to obtain information on the ultrastructural basis of the interactions between neurons in the medulla and those in the intermediolateral nucleus, including SPNs. This integrated approach will provide new information on the functioning of critical cardiovascular regulatory pathways to the spinal cord and may suggest new pharmacologic approaches to controlling arterial pressure.